NM_001017995.3:c.157-7031C>T

Variant names:

• chr5-172413383-G-A
• rs10077897
• NM_001017995.3:c.157-7031C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001017995.3(SH3PXD2B):​c.157-7031C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0657 in 152,254 control chromosomes in the GnomAD database, including 502 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.066 (502 hom., cov: 33)
• Consequence: SH3PXD2B NM_001017995.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.807
• Publications: 1 publications found

Genes affected

SH3PXD2B (HGNC:29242): (SH3 and PX domains 2B) This gene encodes an adapter protein that is characterized by a PX domain and four Src homology 3 domains. The encoded protein is required for podosome formation and is involved in cell adhesion and migration of numerous cell types. Mutations in this gene are the cause of Frank-ter Haar syndrome (FTHS), and also Borrone Dermato-Cardio-Skeletal (BDCS) syndrome. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2015]

SH3PXD2B Gene-Disease associations (from GenCC):

• Frank-Ter Haar syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3PXD2B	NM_001017995.3	c.157-7031C>T		intron_variant	Intron 2 of 12	ENST00000311601.6	NP_001017995.1
SH3PXD2B	NM_001308175.2	c.157-7031C>T		intron_variant	Intron 2 of 12		NP_001295104.1
SH3PXD2B	XM_017009351.2	c.157-7031C>T		intron_variant	Intron 2 of 13		XP_016864840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3PXD2B	ENST00000311601.6	c.157-7031C>T		intron_variant	Intron 2 of 12	1	NM_001017995.3	ENSP00000309714.5
SH3PXD2B	ENST00000519643.5	c.157-7031C>T		intron_variant	Intron 2 of 12	1		ENSP00000430890.1
SH3PXD2B	ENST00000636523.1	c.112-7031C>T		intron_variant	Intron 2 of 13	5		ENSP00000490082.1

Frequencies

GnomAD3 genomes AF: 0.0656 AC: 9982 AN: 152136 Hom.: 499 Cov.: 33

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0412

Gnomad ASJ AF: 0.0671

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00952

Gnomad FIN AF: 0.0302

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0377

Gnomad OTH AF: 0.0616

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0657 AC: 9998 AN: 152254 Hom.: 502 Cov.: 33 AF XY: 0.0617 AC XY: 4595 AN XY: 74444

African (AFR) AF: 0.145 AC: 6034 AN: 41508

American (AMR) AF: 0.0410 AC: 628 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0671 AC: 233 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00932 AC: 45 AN: 4826

European-Finnish (FIN) AF: 0.0302 AC: 320 AN: 10610

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0377 AC: 2566 AN: 68026

Other (OTH) AF: 0.0610 AC: 129 AN: 2116

Alfa AF: 0.0543 Hom.: 66

Bravo AF: 0.0706

Asia WGS AF: 0.0170 AC: 58 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.8
DANN	Benign	0.75
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10077897; hg19: chr5-171840387;